Active, dormant, or on the path to elimination: What does a senescent cell do?

Views of the physiological significance of cellular senescence, a coordinated program activated by cells exposed to stress, have been evolving dramatically in recent years. Senescence involves a cell cycle arrest accompanied by morphologic and metabolic changes, and by enhanced cytokine secretion. There is much evidence to indicate that senescence is central in suppressing tumor development, acting to block the proliferation of cells expressing an active oncogene or suffering from damaged DNA. The detection of senescence in additional settings, including inflammation and wound healing, as well as in aging tissues, suggests that this cellular program is involved in a variety of physiologic processes, mostly associated with pathology. Importantly, however, the fundamental nature of this program remains poorly understood. Does senescence represent a state of dormancy or dysfunction, or do senescent cells play an active, designated role within normal, aging and tumorigenic tissues? Are senescent cells retained within tissues, or are they rapidly removed? Is the function of senescence to counter tissue pathology, or is it an aberrant state primarily contributing to disease? Recent studies of senescence in the in vivo setting have provided some important insights into these questions and have highlighted areas requiring further study.